Benzofuran sübstitüe kalkon türevlerinin insan meme kanseri hücreleri üzerindeki sitotoksik etkilerinin araştırılması
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Date
2019-08-01
Authors
Gündüz, Hülya
Journal Title
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Publisher
Bursa Uludağ Üniversitesi
Abstract
Kanser, genetik ve çevresel koşullar ile hücrelerin kontrolsüz bölünmesi ve çoğalmasıyla ortaya çıkan kompleks bir hastalıktır. Dünya çapında kadınlar arasında meme kanseri en sık görülen ve akciğer kanserinden sonra ölüm oranı en fazla olan kanser türüdür. Meme kanseri için yeni tedavilerin gelişmesine rağmen tedavideki başarı hala tatmin edici değildir. Bu sebeple, meme kanseri hastalarında uygulanabilecek yeni yaklaşımların geliştirilmesi gerekmektedir. Günümüzde kullanılan antikanser ilaçların çoğu bitkisel kökenlidir ve halen yeni etkin bileşikler de araştırılmaktadır. Kalkon türevleri doğada bol miktarda bulunan aromatik bileşiklerdir. Son yıllarda yapılan araştırmalarda, kalkon türevlerin birçok biyolojik aktiviteye sahip olduğu ve kanser tedavisinde umut verici olduğu gösterilmiştir. Dolayısıyla bu tez çalışmasında, sentezi ve karakterizasyonu yapılmış olan iki benzofuran sübstitüe kalkon türevlerinin (Kompleks 1 ve Kompleks 2) antikanser etkileri insan meme kanseri hücre soylarında (MCF-7 ve MDA-MB-231) araştırılmıştır. Komplekslerin hücre canlılığı üzerindeki etkisi 24, 48 ve 72 saat süreyle SRB canlılık testleri ile belirlenmiştir. Sitotoksisite yanıtları ATP canlılık testi ile 48 ve 72 saat süreyle doğrulanmıştır. Komplekslerin sitotoksik aktivitesi sağlıklı insan hücre soyu olan BEAS-2B hücrelerinde de değerlendirilmiştir. Kalkon türevlerin sitotoksik etkilerinden sorumlu hücre ölümünü belirlemek amacıyla floresan boyama (Hoechst 33342 ve PI) yöntemi kullanılmıştır. Komplekslerin hücrelerde yara iyileşmesi üzerine etkileri MDA-MB-231 hücre soyunda araştırılmıştır. Sonuç olarak, benzofuran sübstitüe kalkon türevlerinin MCF-7 ve MDA-MB-231 hücre soylarında doza ve zamana bağlı olarak hücre büyümesini engelledikleri belirlenmiştir. Ayrıca komplekslerin hücrelerde apoptozu indükleyerek, migrasyon yeteneklerinde azalmaya neden olduğu gösterilmiştir. Alınan sonuçlara göre benzofuran sübstitüe kalkon türevlerinin meme kanseri tedavisinde etkili bir ajan olabileceği ve ileri analizlerin yapılması gerektiği sonucuna varılmıştır.
Cancer is a complex disease that causes uncontrolled division and proliferation of cells by genetic and environmental conditions. Among women worldwide, breast cancer is the most common cancer with the highest mortality rate after lung cancer. Despite the recent development of new treatments for breast cancer, it is still not satisfactory. Therefore, new approaches should be developed for breast cancer patients. Herbal natural compounds are important in the treatment of cancer. Chalcohol derivatives are aromatic compounds which are abundant in nature. In recent research, has shown chalcone derivatives have many biological activities and promising in the treatment of cancer. Therefore, in this thesis, the anti-cancer effects of two benzofuran substituted chalcone derivatives (Complex 1 and Complex 2) which were synthesized and characterized were investigated in human breast cancer cell lines (MCF-7 and MDAMB-231). The effect of complexes on cell viability was determined by SRB viability tests for 24, 48 and 72 hours. Cytotoxicity responses were confirmed by ATP viability test for 48 and 72 hours. Cytotoxic activity of complexes was also evaluated in healthy human cell line BEAS-2B cells. Fluorescent staining (Hoechst 33342 and PI) was used for to determine cell death responsible the cytotoxic effects of chalcone derivatives. The effects of complexes on wound healing were investigated in the MDA-MB-231 cell line. As a result, It has been identified benzofuran substituted chalcone derivatives inhibit cell growth time and dose dependent manner in MCF-7 and MDA-MB-231 cell lines. In addition, it has been found that complexes induce apoptosis in cells and cause a decrease in migration ability. According to the results, it was concluded that benzofuran substituted chalcone derivatives can be an effective agent in the treatment of breast cancer and further analysis should be performed.
Cancer is a complex disease that causes uncontrolled division and proliferation of cells by genetic and environmental conditions. Among women worldwide, breast cancer is the most common cancer with the highest mortality rate after lung cancer. Despite the recent development of new treatments for breast cancer, it is still not satisfactory. Therefore, new approaches should be developed for breast cancer patients. Herbal natural compounds are important in the treatment of cancer. Chalcohol derivatives are aromatic compounds which are abundant in nature. In recent research, has shown chalcone derivatives have many biological activities and promising in the treatment of cancer. Therefore, in this thesis, the anti-cancer effects of two benzofuran substituted chalcone derivatives (Complex 1 and Complex 2) which were synthesized and characterized were investigated in human breast cancer cell lines (MCF-7 and MDAMB-231). The effect of complexes on cell viability was determined by SRB viability tests for 24, 48 and 72 hours. Cytotoxicity responses were confirmed by ATP viability test for 48 and 72 hours. Cytotoxic activity of complexes was also evaluated in healthy human cell line BEAS-2B cells. Fluorescent staining (Hoechst 33342 and PI) was used for to determine cell death responsible the cytotoxic effects of chalcone derivatives. The effects of complexes on wound healing were investigated in the MDA-MB-231 cell line. As a result, It has been identified benzofuran substituted chalcone derivatives inhibit cell growth time and dose dependent manner in MCF-7 and MDA-MB-231 cell lines. In addition, it has been found that complexes induce apoptosis in cells and cause a decrease in migration ability. According to the results, it was concluded that benzofuran substituted chalcone derivatives can be an effective agent in the treatment of breast cancer and further analysis should be performed.
Description
Keywords
Meme kanseri, Kalkonlar, Sitotoksite, Breast cancer, Chalcones, Cytotoxicity
Citation
Gündüz, H. (2019). Benzofuran sübstitüe kalkon türevlerinin insan meme kanseri hücreleri üzerindeki sitotoksik etkilerinin araştırılması. Yayınlanmamış yüksek lisans tezi. Bursa Uludağ Üniversitesi Fen Bilimleri Enstitüsü.